Menopausal age does not affect ventricular structure and function: a Mendelian randomization study

Abstract

Objectives

Observational studies have suggested an association between age at natural menopause (ANM) and ventricular structure and function. Nevertheless, the causal relationship remains unclear. This study aimed to evaluate the causal effects of ANM on ventricular structure and function by Mendelian randomization (MR) analysis.

Methods

Genome-wide association summary statistics for ANM and 16 ventricular structures and functions were obtained. The inverse variance weighted (IVW) method was the primary MR approach for assessing causal associations. In addition, three additional MR methods (MR-Egger, weighted median and weighted mode) were performed to complement the IVW method. Furthermore, various sensitivity tests were conducted to evaluate the reliability of the MR results.

Results

The IVW method identified no causal association between ANM and all 16 ventricular structures or functions (p > 0.05). Three additional MR methods yielded parallel results to the IVW approach (p > 0.05). Various sensitivity tests revealed stability of the MR results, indicating no heterogeneity or horizontal pleiotropy.

Conclusion

The present MR study indicated that ANM would not causally affect ventricular structure or function. Therefore, the correlation between ANM and ventricular characteristics in previous observational studies might be attributed to shared upstream cardiovascular risk factors or unidentified genetic mutations that simultaneously affect both ANM and ventricular structure and function.

Keywords:

• Menopause
• heart ventricles
• Mendelian randomization
• causal relationship
• ovarian aging
• cardiovascular diseases
• heart

Acknowledgements

The authors thank the ReproGen consortium (https://www.reprogen.org/) and GWAS Catalog platform (https://www.ebi.ac.uk/gwas/) for providing GWAS summary-level statistics.

Disclosure statement

No potential conflict of interest was reported by the authors.